The expression of activated cellular oncogenes in chemically-induced tumors in rodents (rats, mice, and Syrian hamsters) and in selected human neoplasms including ovary uterine endometrium, and prostate, and the relationship of oncogene expression to progression from the normal to a neoplastic phenotype are being studied by transfection of NIH 3T3 and SHOK cells and by hybridization techniques including oligonucleotide probing for specific point mutations. Polymerase chain reaction (PCR) techniques are being employed to amplify selected genomic segments in order to search for subpopulations of cells in a given tissue in which activating oncogene mutations may be present. In collaboration with the Inorganic Carcinogenesis Section (see Project Z01CP04582), the especially important finding has been made that renal tumors induced in rats by the carcinogenic metal, nickel, in the form of nickel subsulfide contain a specific activating GGT to GTT transversion in codon 12 of the K-ras cellular protooncogene, providing the first evidence implicating a genotoxic mechanism involving known transforming genes in neoplastic transformation by this class of carcinogenic agents.